Cancer Cells Grow by Altering the Gut Microbiome

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Leukemia reduces the numbers of blood glucose-regulating gut bacteria in order to grow, according to a compelling new study.

Cancer incidence rates have long been associated with obesity and diabetes. Although there is no convincing evidence connecting an increased risk of cancer directly to sugar consumption, a growing body of research suggests it is likely.

Glucose, a type of sugar, is an important source of energy for the cells in our body (especially the brain), and cancer cells need a consistent source of glucose to grow. For to tumors to grow aggressively, they must divert glucose away from other (normal) cells and stimulate the body to make more.

Now, using a mouse model, researchers at the University of Colorado Cancer Center have identified two new ways that leukemia alters the body's metabolism to help it grow.

The cancer causes a diabetes-like condition, which diverts glucose from normal cells and makes it available to the tumor.

In the first mechanism, cancer cells stimulate fat cells to overproduce a protein called IGFBP1. This makes the fat cells more sensitive to insulin, meaning they use less and leave more available for the tumor.

The second mechanism serves to keep the body’s insulin production low to stop it from responding to the shortages triggered by the first strategy.

The researchers discovered this by studying the gut microbiome, identifying differences in microbiome composition between healthy mice and animals with leukemia.

The main change they saw in the gut microbiomes of mice with leukemia was a reduction in bacteria that produce short-chain fatty acids, which are essential for gut health.

Another change involves the inactivation of hormones called incretins. These hormones are released by the gut and reduce the level of blood glucose in our system after we eat.

Together, these mechanisms favor the cancer by altering how the body uses energy.

Interestingly, the researchers found that they could extend the lives of the leukemic mice by rebalancing the glucose regulation and slowing the tumor’s growth.

This research doesn’t suggest that removing sugar from a diet will have an effect on cancer growth but does illuminate how cancer steals energy resources. Hopefully, scientists can use this information to develop new strategies (potential through the microbiome) to prevent cancers from obtaining the energy they need to grow.

Reference:

Ye, Haobin, et al. "Subversion of Systemic Glucose Metabolism as a Mechanism to Support the Growth of Leukemia Cells." Cancer Cell (2018). doi: https://doi.org/10.1016/j.ccell.2018.08.016